Case Study – Applying the FAIR Shake™

Since the suicide death of Dan Markingson in May of 2004, there has been a lot of debate as to whether or not the 26 year old psychiatric patient should have been approached to consent to participate in a clinical research trial for the comparison of three atypical antipsychotic drugs. Recently, there has been an article published in the Minnesota Dailyabout a petition signed by over 3,000 ethicists, researchers and scholars asking the University of Minnesota’s President to review the case to prevent future tragedies at the institution. Such a petition was created due to several errors in processes related to human subject protection.

A summary of the story follows. During a visit to his mother in Minnesota, Dan starting exhibiting “strange” behavior and even threatened to slay his mother. Dan was committed to an inpatient psychiatric unit at the University of Minnesota after the evaluation by a psychiatrist at the University and by a court appointed clinical psychologist. Dan was delusional, threatened homicide and denied he had a mental illness. The court had ruled that Dan did not have the mental capacity to make decisions about his own care and ordered a stay of commitment to the psychiatric unit at the University of Minnesota for a six-month period. Two days after Dan’s commitment, his psychiatrist and a social worker completed an evaluation of Dan that had declared him competent. His psychiatrist immediately filed a petition to the court to lift the stay of commitment order. The same day that the evaluation was completed at the University of Minnesota, but before the court could re-evaluate or review Dan’s case in order to lift the stay commitment order, Dan was consented and enrolled into a clinical research trial to compare atypical antipsychotic drugs. Incidentally, his psychiatrist was the Principal Investigator and his social worker was the Research Coordinator for the trial. After being enrolled in the trial, Dan’s sanity and mental capability continued to deteriorate and he eventually committed suicide.

Without knowing the logistics or the details of the entire case, or knowing the Minnesota laws regarding a stay of commitment court order, there is a question that comes to the mind of an IMARC monitor that reviews the informed consent process at every site encountered. Did the enrollment of this subject take place according to the FAIR Shake™ technique?

F: Federal RegulationsWas the informed consent obtained according to the Federal Regulations 21 CRF 50?The federal regulations provides a detailed guideline as to the general requirements of the informed consent (21 CRF 50.20), the basic elements that should be physically present within the document (21 CRF 50.25) and the documentation of the informed consent process (21 CRF 50.27).

A: AgreementDid the Principal Investigator abide by the elements within Agreement that he or she signed, the Form FDA 1572? Before participating in any drug trial, the investigator must complete the Form FDA 1572 (21 CRF 312.53). The 1572 provides the investigator’s and the site’s qualification to the Sponsor to assist in documenting that they are qualified to conduct the study. Additionally, this document informs the investigator of his or her responsibilities regarding the study and by signing; the investigator agrees to comply with FDA regulations.

I: Investigation Plan (protocol)Has the protocol been reviewed in detail by the study staff? Being a trial investigating antipsychotic medications for patients with a first episode of schizophrenia, what are the inclusion and exclusion criteria for enrollment into the study? A protocol is written plan as to how the study will be conducted in detail. It is a step by step set of instructions that must be followed exactly to ensure the safety of the subject. All study staff should know the inclusion and exclusion criteria inside and out before enrolling a subject.

R: Requirements of the IRBWhat is the IRB’s policy regarding the informed consent process and vulnerable population? The FDA delegated the task of protecting the rights and welfare of human subjects (21 CRF 56.101) to the IRB. There are policies in place by the IRB to accomplish just this. The study personnel should know the IRB’s policy around consenting and follow the rules set to ensure the consent process is conducted properly. An IRB should have safeguards in place to protect the vulnerable population which includes children, prisoners, pregnant women or the mentally disabled (21 CRF 56.111), so that they are not coerced or influenced to participate in research.

Obtaining consent is more then a document, it is a process. This process involves many intricate parts that are in place by the federal government, the agreement signed by the investigator, the protocol written by the Sponsor and the IRB; all for one goal- to keep the subject safe!

What are your thoughts regarding the consenting of subjects that are bound under a “stay of commitment” court order to an inpatient psychiatric facility?

FYI…After Dan’s death, the Minnesota House of Representatives passes a law on 1 August 2009 nicknamed “Dan’s Law”. This law prohibits the enrollment of psychiatric patients into drug trials while being under a commitment order to an inpatient psychiatric facility. Furthermore, the law explains that if a trial would be beneficial to the patient under a commitment order, an affidavit must be submitted to the court and the primary psychiatrist that is treating the patient must not be involved in the trial.